The Application of Consensus Weighted Gene Co-expression NetworkAnalysis in Celiac Disease: Identification of Potential Protective Genes and Pathways

Celiac disease (CeD) is an autoimmune enteropathy triggered by dietary gluten. Almost ۹۰% of CeD patients have HLA-DQ۲ or -DQ۸ haplotypes. As a high proportion of first-degree relatives (FDRs) of CeD patients have the same haplotype, it is assumed that they are at a higher risk of disease development than the general population. Nevertheless, the prevalence of CeD among FDRs is considerably low (۷.۵%). Methods:In order to figure out this discrepancy, a microarray dataset of intestinal mucosal biopsies of CeD patient, FDR, and control groups was reanalyzed, and gene co-expression network using WGCNA was constructed. Di↵erentially expressed genes in the opposite modules from consensus analysis were obtained. The functional enrichment analysis were carried out.Results:WGCNA analysis identified ۱۰ consensus modules associated with CeD and FDR groups, including ۵ modules with opposite correlation. Among the genes of opposing modules, there were a total of ۱۳۶۹ DEGs, ۱۵۹ of which were common between FDR and CeD groups. Functional enrichment analysis revealed potential pathways and candidate genes involved in the host energy metabolism, programmed cell death, actin folding, and antigen cross presentation that might play a compensatory protective e↵ect in the intestinal mucosa of celiac FDR. Conclusions: In current study, our result determined some genes and pathways with protective functions in FDR groups. These genes and molecular mechanisms could be a matter of investigation as potential druggable targets or prognostic markers in CeD.

کلیدواژه ها:

Celiac Disease ، WGCNA ، Protein-Protein Interaction network ، Transcriptome ، Systems Biology